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Next-Generation Sequencing Expanded NGS List

Mutations (DNA) ABI1 BRD4 CRLF2 FOXO4 HOXC11 MUC1 PAK3 RHOH TAL2 ABL1 BTG1 DDB2 FSTL3 HOXC13 KLK2 MUTYH PATZ1 RNF213 TBL1XR1 ACKR3 BTK DDIT3 GATA1 HOXD11 LASP1 MYCL (MYCL1) PAX8 RPL10 TCEA1 AKT1 C15orf65 DNM2 GATA2 HOXD13 LMO1 NBN PDE4DIP SEPT5 TCL1A ® AMER1 (FAM123B) CBLC DNMT3A GNA11 HRAS LMO2 NDRG1 PHF6 SEPT6 TERT Tumor Profiling Services from Caris Molecular Intelligence AR CD79B EIF4A2 GPC3 IKBKE MAFB NKX2-1 PHOX2B SFPQ TFE3 ARAF CDH1 ELF4 HEY1 INHBA MAX NONO PIK3CG SLC45A3 TFPT ATP2B3 CDK12 ELN HIST1H3B IRS2 MECOM NOTCH1 PLAG1 SMARCA4 THRAP3 ATRX CDKN2B ERCC1 HIST1H4I JUN MED12 NRAS PMS1 SOCS1 TLX3 BCL11B CDKN2C ETV4 HLF KAT6A (MYST3) MKL1 NUMA1 POU5F1 TMPRSS2 BCL2 CEBPA FAM46C HMGN2P46 KAT6B MLLT11 NUTM2B PPP2R1A SPOP UBR5 Next-Generation BCL2L2 CHCHD7 FANCF HNF1A KCNJ5 MN1 OLIG2 PRF1 SRC VHL Sequencing BCOR CNOT3 FEV HOXA11 KDM5C MPL OMD PRKDC SSX1 WAS Multi-platform, solid tumor BCORL1 COL1A1 FOXL2 HOXA13 KDM6A MSN P2RY8 RAD21 STAG2 ZBTB16 Next-Generation Sequencing for BRD3 COX6C FOXO3 HOXA9 KDSR MTCP1 PAFAH1B2 RECQL4 TAL1 ZRSR2 analysis for therapeutic decision support additional biomarker analysis and Copy Number Variations (DNA) ABL2 BRCA21 COPB1 ESR1 FUS KIT MYB PER1 RUNX1 TFG ACSL3 BRIP1 CREB1 ETV1 GAS7 KLHL6 PICALM RUNX1T1 TFRC Chemotherapy 4 – ACSL6 BUB1B CREB3L1 ETV5 GATA3 KMT2A (MLL) MYCN PIK3CA SBDS TGFBR2 AFF1 C11orf30 (EMSY) CREB3L2 ETV6 GID4 (C17orf39) KMT2C (MLL3) MYD88 PIK3R1 SDC4 TLX1 Immunotherapy 4 – AFF3 C2orf44 CREBBP EWSR1 GMPS KMT2D (MLL2) MYH11 PIK3R2 SDHAF2 TNFAIP3 AFF4 CACNA1D CRKL EXT1 GNA13 KRAS MYH9 PIM1 SDHB TNFRSF14 Targeted Therapy 4 4 AKAP9 CALR CRTC1 EXT2 GNAQ KTN1 NACA PML SDHC TNFRSF17 AKT2 CAMTA1 CRTC3 EZH2 GNAS LCK NCKIPSD PMS2 SDHD TOP1 Expression via IHC 4 – AKT3 CANT1 CSF1R EZR GOLGA5 LCP1 NCOA1 POLE SEPT9 TP53 ALDH2 CARD11 CSF3R FANCA GOPC LGR5 NCOA2 POT1 SET TPM3 DNA Analysis via Pyro Sequencing 4 – ALK CARS CTCF FANCC GPHN LHFP NCOA4 POU2AF1 SETBP1 TPM4 DNA/RNA Analysis APC CASC5 CTLA4 FANCD2 GPR124 LIFR NF1 PPARG SETD2 TPR 4 – ARFRP1 CASP8 CTNNA1 FANCE GRIN2A LPP NF2 PRCC SF3B1 TRAF7 via Fragment Analysis ARHGAP26 CBFA2T3 CTNNB1 FANCG GSK3B LRIG3 NFE2L2 PRDM1 SH2B3 TRIM26 Molecular Analysis ARHGEF12 CBFB CYLD FANCL H3F3A LRP1B NFIB PRDM16 SH3GL1 TRIM27 592 592 Genes ARID1A CBL CYP2D6 FAS H3F3B LYL1 NFKB2 PRKAR1A SLC34A2 TRIM33 via Next-Generation Sequencing ARID2 CBLB DAXX FBXO11 HERPUD1 MAF NFKBIA PRRX1 SMAD2 TRIP11 ARNT CCDC6 DDR2 FBXW7 HGF MALT1 NIN PSIP1 SMAD4 TRRAP Clinical Trial Opportunities 4 4 ASPSCR1 CCNB1IP1 DDX10 FCRL4 HIP1 MAML2 NOTCH2 PTCH1 SMARCB1 TSC1 ASXL1 CCND1 DDX5 FGF10 HMGA1 MAP2K1 NPM1 PTEN SMARCE1 TSC2 ATF1 CCND2 DDX6 FGF14 HMGA2 MAP2K2 NR4A3 PTPN11 SMO TSHR ATIC CCND3 DEK FGF19 HNRNPA2B1 MAP2K4 NSD1 PTPRC SNX29 TTL ATM CCNE1 DICER1 FGF23 HOOK3 MAP3K1 NT5C2 RABEP1 SOX10 U2AF1 Technical Specifications ATP1A1 CD274 (PDL1) DOT1L FGF3 HSP90AA1 MCL1 NTRK1 RAC1 SPECC1 USP6 ATR CD74 EBF1 FGF4 HSP90AB1 NTRK2 RAD50 SPEN VEGFA AURKA CD79A ECT2L FGF6 IDH1 MDM4 NTRK3 RAD51 SRGAP3 VEGFB Sufficient tumor must be present to complete all analysis. If you have any questions, please contact Client Services at (888) 979-8669. AURKB CDC73 EGFR FGFR1 IDH2 MDS2 NUP214 RAD51B SRSF2 VTI1A AXIN1 CDH11 ELK4 FGFR1OP IGF1R MEF2B NUP93 RAF1 SRSF3 WHSC1 Technical Information IHC CISH FISH AXL CDK4 ELL FGFR2 IKZF1 MEN1 NUP98 RALGDS SS18 WHSC1L1 BAP1 CDK6 EML4 FGFR3 IL2 MET (cMET) NUTM1 RANBP17 SS18L1 WIF1 1 unstained slide at 4μm thickness from FFPE 1 unstained slide at 4μm thickness from FFPE 2 unstained slides at 4μm thickness from FFPE Sample Requirements BARD1 CDK8 EP300 FGFR4 IL21R MITF PALB2 RAP1GDS1 STAT3 WISP3 block, with evaluable tumor present, per block, with at least 20-100 evaluable tumor block, with at least 100 evaluable cells present (see requsition for full details) BCL10 CDKN1B EPHA3 FH IL6ST MLF1 PAX3 RARA STAT4 WRN IHC test cells present, per CISH test and 10% tumor, per FISH test BCL11A CDKN2A EPHA5 FHIT IL7R MLH1 PAX5 RB1 STAT5B WT1 BCL2L11 CDX2 EPHB1 FIP1L1 IRF4 MLLT1 PAX7 RBM15 STIL WWTR1 Sensitivity/Specificity >95% >95% >95% BCL3 CHEK1 EPS15 FLCN ITK MLLT10 PBRM1 REL STK11 XPA BCL6 CHEK2 ERBB2 (HER2) FLI1 JAK1 MLLT3 PBX1 RET SUFU XPC BCL7A CHIC2 ERBB3 (HER3) FLT1 JAK2 MLLT4 PCM1 RICTOR SUZ12 XPO1 Next-Generation Sequencing BCL9 CHN1 ERBB4 (HER4) FLT3 JAK3 MLLT6 PCSK7 RMI2 SYK YWHAE Technical Information BCR CIC ERC1 FLT4 JAZF1 MNX1 PDCD1 (PD1) RNF43 TAF15 ZMYM2 Mutations and Copy Number Variations (DNA) Fusions (RNA) BIRC3 CIITA ERCC2 FNBP1 KDM5A MRE11A PDCD1LG2 (PDL2) ROS1 TCF12 ZNF217 BLM CLP1 ERCC3 FOXA1 KDR (VEGFR2) MSH2 PDGFB RPL22 TCF3 ZNF331 FFPE block or 15 unstained slides with a minimum of 20% FFPE block or 2-5 unstained slides with a minimum of 20% Sample Requirements BMPR1A CLTC ERCC4 FOXO1 KEAP1 MSH6 PDGFRA RPL5 TCF7L2 ZNF384 malignant origin. Needle biopsy is also acceptable (4-6 cores). malignant origin. Needle biopsy is also acceptable (4-6 cores). BRAF CLTCL1 ERCC5 FOXP1 KIAA1549 MSI2 PDGFRB RPN1 TET1 ZNF521 BRCA11 CNBP ERG FUBP1 KIF5B MTOR PDK1 RPTOR TET2 ZNF703 Tumor Enrichment Microdissection performed on all cases resulting in ~25% increase in tumor nuclei and enhances detection of minor clonal variants CNTRL TFEB Gene Fusions (RNA) Variant Transcripts (RNA) Amount of DNA Required 200ng input (50ng)

MET Exon 14 ALK BRAF NTRK1 NTRK2 NTRK3 RET ROS1 RSPO3 EGFR vIII Skipping PPV >99% >98% > 99% for base substitutions at ≥ 5% mutant allele frequency; 1 May not be available for Medicare patients. Medicare reimburses BRCA1-2 for breast and ovarian cases only. Sensitivity > 99% for indels at ≥ 5% mutant allele frequency; >91% Next-Generation Sequencing may not be available in New York State. For testing available in New York, please view >95% for copy number variations (amplifications ≥ 8 copies) the online New York Profile Menu (www.CarisMolecularIntelligence.com/solid_tumors-NY). Average Depth of Coverage (DNA) >750X >30,000 Unique RNA Fragments Average Depth/Count (RNA) To order or learn more, visit www.CarisMolecularIntelligence.com. Number of Genes 592 genes 10 genes US: 888.979.8669 | [email protected] Caris Molecular Intelligence is a trademark of Caris Life Sciences. Intl: 00 41 21 533 53 00 | [email protected] © 2016 Caris Life Sciences. All rights reserved. TN0276 v5 December 14, 2016 Caris Molecular Intelligence®Associations List Biomarker Analysis by Tumor Type

The list below details the biomarkers assessed, technology platforms utilized and associated therapies or clinical trials. The information below details the biomarkers analyzed by technology for the tumor type submitted. Before ordering Biomarkers and therapy associations may vary by the tumor type submitted. The current and definitive list menu can be testing services, please refer to the profile menu online (www.CarisMolecularIntelligence.com/profilemenu) to view the found online at www.CarisMolecularIntelligence.com/profilemenu. most up-to-date listing of biomarkers that will be performed. Tests may vary if insufficient tumor samples are submitted.

Individual assay results are always included with the final report. MI Profile™ Agent Biomarker Platform Agent Biomarker Platform Next-Generation Sequencing (NGS) EGFR NGS ER Tumor Type Immunohistochemistry (IHC) (see reverse for gene list) Other afatinib (assoc. in Breast only) IHC (assoc. in NSCLC only) ERBB2 (Her2) NGS Mutation everolimus, temsirolimus PIK3CA NGS Mutation ERCC1, PD-L1, RRM1, TOP2A, TRKA/B/C (NTRK), (excluding CRC) Bladder Mutation, CNV Analysis (DNA) afatinib + EGFR T790M NGS Mutation TS, TUBB3 (combination assoc. in NSCLC only) exemestane + everolimus, fulvestrant, ER IHC IHC; NGS Fusion Analysis AR, ER, ERCC1, Her2/Neu, PD-L1, PR, PTEN, TOPO1, TOP2A (Chromogenic in situ alectinib, ceritinib ALK pabociclib combination therapy ESR1 NGS Mutation Breast Mutation, CNV Analysis (DNA) (RNA) TRKA/B/C (NTRK), TS Hybridization) gemcitabine RRM1 IHC aspirin PIK3CA NGS Mutation of Unknown ERCC1, PD-L1, RRM1, TOPO1, TRKA/B/C (NTRK), (assoc. in CRC only) Mutation, CNV Analysis (DNA) AR IHC Primary TS, TUBB3 atezolizumab PD-L1 IHC (assoc. in NSCLC only) ER, ERCC1, PD-L1, PR, RRM1, TOP2A, TOPO1, hormone therapies3 ER IHC Cervix Mutation, CNV Analysis (DNA) cabozantinib RET NGS Fusion Analysis (RNA) TRKA/B/C (NTRK), TS, TUBB3 capecitabine, fluorouracil, pemetrexed TS IHC PR IHC Cholangiocarcinoma/ ERCC1, Her2/Neu, PD-L1, RRM1, TOPO1, Mutation, CNV Analysis (DNA) ATM NGS Mutation cKIT NGS Mutation Hepatobiliary TRKA/B/C (NTRK), TS, TUBB3 BRCA11 NGS Mutation imatinib ERCC1, MLH1, MSH2, MSH6, PD-L1, PMS2, PTEN, carboplatin, cisplatin, oxaliplatin PDGFRA NGS Mutation Colorectal Mutation, CNV Analysis (DNA) MSI1 (Fragment Analysis) BRCA21 NGS Mutation TOPO1, TRKA/B/C (NTRK), TS irinotecan ER, ERCC1, MLH1, MSH2, MSH6, PMS2, PR, PD-L1, PTEN, ERCC1 IHC TOPO1 IHC Endometrial Mutation, CNV Analysis (DNA) MSI1 (Fragment Analysis) topotecan RRM1, TOP2A, TOPO1, TRKA/B/C (NTRK), TS, TUBB3 BRAF NGS Mutation (excluding Breast, CRC, NSCLC) ERCC1, Her2/Neu, PD-L1, TOP2A, TOPO1, KRAS NGS Mutation Gastric Mutation, CNV Analysis (DNA) lapatinib, pertuzumab, T-DM1 Her2/Neu NGS CNV (DNA) TRKA/B/C (NTRK), TS, TUBB3 cetuximab, panitumumab2 NRAS NGS Mutation 1 (assoc. in CRC only) BRCA1 PIK3CA NGS Mutation mitomycin-c NGS Mutation GIST PD-L1, PTEN, TRKA/B/C (NTRK) Mutation, CNV Analysis (DNA) BRCA21 PTEN IHC Mutation, CNV (DNA); MGMT Methylation PD-L1 IHC Glioma ERCC1, PD-L1, TOPO1 cetuximab EGFR NGS CNV nivolumab, pembrolizumab Fusion Analysis (RNA) (Pyrosequencing) (assoc. in Bladder, Kidney, , NSCLC only) MSI IHC; NGS Mutation (DNA) & (pembrolizumab only) FA ALK Fusion Analysis (RNA) Head & Neck ERCC1, PD-L1, RRM1, TRKA/B/C (NTRK), TS, TUBB3 Mutation, CNV Analysis (DNA) ATM cMET NGS Mutation, CNV (DNA) (assoc. in Prostate only) olaparib BRCA11 NGS Mutation Kidney ERCC1, PD-L1, RRM1, TOP2A, TRKA/B/C (NTRK), TUBB3 Mutation, CNV Analysis (DNA) ROS1 NGS Fusion Analysis (RNA) BRCA21 dabrafenib, vemurafenib2 BRAF NGS Mutation Melanoma ERCC1, MGMT, PD-L1, TRKA/B/C (NTRK), TUBB3 Mutation, CNV Analysis (DNA) osimertinib MGMT IHC EGFR T790M NGS Mutation (assoc. in NSCLC only) Neuroendocrine/ ERCC1, PD-L1, MGMT, TOP2A, TS Mutation, CNV Analysis (DNA) dacarbazine, temozolomide MGMT-Methylation Pyrosequencing ER IHC Small Cell Lung palbociclib IDH1(assoc. in NGS (assoc. in Breast only) ALK, ERCC1, PD-L1, PTEN, RRM1, TOPO1, Mutation, CNV (DNA); High Grade Glioma only) Her2/Neu IHC Non-Small Cell Lung TRKA/B/C (NTRK), TS, TUBB3 Fusion Analysis (RNA) docetaxel, paclitaxel, nab-paclitaxel TUBB3 IHC sunitinib cKIT NGS (assoc. in GIST only) ER, ERCC1, PD-L1, PR, RRM1, TOP2A, TOPO1, IHC Ovarian Mutation, CNV Analysis (DNA) doxorubicin, 2 TRKA/B/C (NTRK), TUBB3 TOP2A trametinib BRAF NGS liposomal-doxorubicin, epirubicin (assoc. in Melanoma only) CISH ERCC1, MLH1, MSH2, MSH6, PD-L1, PMS2, RRM1, ERBB2 (Her2) Pancreatic Mutation, CNV Analysis (DNA) AR (assoc. in NSCLC only) NGS TOPO1, TRKA/B/C (NTRK), TS, TUBB3 enzalutamide, bicalutamide (assoc. in TNBC only) IHC EGFR NGS Mutation Her2/Neu IHC; NGS CNV (DNA) Prostate AR, ERCC1, PD-L1, TRKA/B/C (NTRK), TUBB3 Mutation, CNV Analysis (DNA) trastuzumab KRAS NGS Mutation PTEN IHC (assoc. in Breast only) ERCC1, MGMT, PD-L1, RRM1, TOP2A, TOPO1, , PIK3CA NGS Mutation Sarcoma Mutation, CNV Analysis (DNA) (assoc. in NSCLC only) PIK3CA NGS Mutation TRKA/B/C (NTRK), TUBB3 cMET NGS CNV (DNA) (assoc. in Breast only) NGS Mutation (DNA) & Thyroid ERCC1, PD-L1, TOP2A, TRKA/B/C (NTRK) Mutation, CNV Analysis (DNA) PTEN IHC vandetanib RET Fusion Analysis (RNA) ERCC1, PD-L1, RRM1, TOP2A, TRKA/B/C (NTRK), IHC: Immunohistochemistry CISH: Chromogenic in situ Hybridization FA: Fragment Analysis Other Tumors Mutation, CNV Analysis (DNA) TS, TUBB3 NGS: Next-Generation Sequencing CNV: Copy Number Variation by NGS FUS: Fusion Analysis by NGS

Note: Biomarkers listed above may also be assessed for clinical trial opportunities and may include clinical trials associations. In certain instances, some biomarkers included in MI Profile or genes ordered individually will not associate with commercially available cancer therapies or clinical trials. For PD-L1 IHC testing, Dako antibody 22c3 is available upon request. 1 May not be available for Medicare patients. Medicare reimburses BRCA1-2 for breast and ovarian cases only. 1 I f MSI is ordered and the tumor percentage is 20-49% or MSI testing is not possible, MMR IHCs (MLH1, MSH2, MSH6, PMS2) will be performed. 2 In CRC, cetuximab/, vemurafenib/dabrafenib, and trametinib may be reported in combination. 3 Hormone therapies may include: tamoxifen, toremifene, fulvestrant, letrozole, anastrozole, exemestane, megestrol acetate, leuprolide, goserelin, bicalutamide, flutamide, abiraterone, enzalutamide, triptorelin, abarelix, degarelix.